Genomic imbalances in craniofacial microsomia.

Area of Science:

• Genetics
• Medical Genomics
• Developmental Biology

Background:

• Craniofacial microsomia (CFM) is a complex congenital condition affecting facial development.
• Genomic imbalances, including copy number variants (CNVs), are increasingly recognized as contributors to CFM.
• Previous studies suggest a link between CFM and specific genetic alterations, but comprehensive screening is often lacking.

Purpose of the Study:

• To investigate the prevalence of 22q11.2 deletions and other genomic imbalances in individuals with CFM.
• To identify pathogenic CNVs and variants of unknown significance (VOUS) in CFM patients using advanced molecular techniques.
• To correlate the presence of genomic alterations with additional major clinical features in CFM.

Main Methods:

• Clinical evaluation by a geneticist for 54 individuals diagnosed with CFM.
• Multiplex ligation-dependent probe amplification (MLPA) for 22q11.2 deletion screening in all participants.
• Chromosomal microarray analysis (CMA) for individuals presenting with additional major features.

Main Results:

• Pathogenic CNVs in the 22q11.2 region were detected in 5.6% of CFM patients via MLPA.
• CMA identified pathogenic CNVs in 23.5% of analyzed cases, including alterations at 2p12, 5p15, 13q13, and 22q11.
• All individuals with pathogenic CNVs exhibited additional major features, most commonly congenital heart disease (CHD).

Conclusions:

• Genomic imbalances, particularly CNVs, are present in a significant subset of CFM patients.
• The presence of additional major features, such as CHD, warrants thorough investigation for CNVs.
• Comprehensive genetic screening, including CMA, is recommended for CFM patients with associated anomalies.